The present invention relates to apparatus and method for use in non-invasively determining a condition of the circulatory system of a subject. More particularly, the present invention is directed to an apparatus and method for non-invasively determining the functional cardiac output of the heart.
The physiological function of the heart is to circulate blood through the circulatory system to the body and lungs. For this purpose, the heart receives blood in arterial chambers during its relaxed or diastolic phase and discharges blood from its ventricle chambers during the contractile or systolic phase. The amount of blood discharged from a ventricle chamber of the heart per unit time is the cardiac output (CO). A typical cardiac output for the heart of a normal adult (at rest) is 5-6 liters per minute.
During circulation through the body, the blood is depleted of oxygen (O2) and is enriched with carbon dioxide (CO2) as a result of the metabolic activity of the body. A major purpose for blood circulation is to take venous blood that has been depleted in O2 and enriched in CO2 as a result of its passage through the tissues of the body and supply it to the lungs. In the alveoli of the lungs, O2 is supplied to the blood from the breathing gases, typically air, and CO2 is discharged into the breathing gases. The oxygenated arterial blood is then supplied to the body tissues. The gas exchange takes place in the capillaries of the lung because of the differences in concentration, or partial pressure, of O2 and CO2 in breathing gases, such as air, and in the venous blood. That is, the blood is low in O2 and high in CO2 whereas air is high in O2 and low in CO2.
A common condition reducing the gas exchange efficiency of the lungs is the presence of shunt perfusion or blood flow in the lungs. A shunt comprises pulmonary blood flow that does not engage in gas exchange with breathing gases, due to blockage or constriction in alveolar gas passages, or for other reasons. This shunt blood flow thus bypasses normal alveoli in which gas exchange is carried out. Upon leaving the lungs, the shunt blood flow mixes with the non-shunt blood flow. The former reduces the oxygen content and increases the CO2 content in the mixed arterial blood supplied to the body tissues.
It will be appreciated that only the non-shunt pulmonary blood flow through the lungs participates in the gas exchange function of the lungs and in oxygenation and CO2 removal in the blood of the subject. The quantity of blood that participates in such pulmonary gas exchange in the lungs is termed functional cardiac output (FCO). For diagnostic or other purposes, it is frequently desirable or essential to know this quantity.
While shunt conditions can occur in the lungs due to blockage brought about by disease, mechanical ventilation, particularly when the respiratory muscles of a subject are relaxed as during anesthesia, can result in an increase in the pulmonary shunt. The breathing gases supplied to the lungs can be enriched with oxygen under such conditions to assist in oxygenation of the blood. However, a sufficient amount of CO2 may not be removed from the blood when the pulmonary shunt is increased, giving rise to potentially adverse consequences to the subject.
The classic technique for determining the functional cardiac output of the heart is through use of the Fick equation                     FCO        =                              VCO            2                                              CvCO              2                        -                          CcCO              2                                                          (        1        )            where,                VCO2 in ml/min. is the amount of CO2 released from the blood in the circulatory system of the subject,        CvCO2 is the mixed venous blood CO2 content, for example in ml CO2/ml of blood, and        CcCO2 is the end capillary blood CO2 content, i.e. the CO2 content in the blood leaving the ventilated lungs.        
The Fick equation states that, knowing the amount of CO2 gas released from the blood in a unit of time (e.g. the rate of gas transfer as a volume/minute) and the concurrent gas transfer occurring per unit of blood (i.e. volume of gas/volume of blood), the blood flow through the lungs (i.e. FCO expressed in volume/minute) can be determined.
If a portion of the pulmonary blood flow of the subject is in shunt, this will decrease the amount of CO2 released from the blood and the computation of Equation (1) provides an indication of the resulting decrease in functional cardiac output. In computing functional cardiac output using the Fick equation, the quantity VCO2 can be determined non-invasively by subtracting the amount of CO2 of the inhaled breathing gases, for example air, from the amount of CO2 of the exhaled breathing gases, taking into account changes in the amount of CO2 stored in the lungs and the deadspace in the breathing organs of the subject, such as the trachea and bronchi. The amount of CO2 stored in the lungs can be computed from the alveolar CO2 gas concentration, as determined from an end tidal breathing gas measurement, and the end expiratory volume VEE of the lungs. The end capillary blood CO2 content (CcCO2) can be determined non-invasively, with a fair degree of accuracy, from a measurement of the concentration of CO2 in the breathing gases exhaled at the end of the expiration of a tidal breathing gas volume, i.e. the end tidal (ET) CO2 level. See also Respiratory Physiology, by J. F. Nunn, published 1993 by Butterworths.
The venous blood CO2 content (CvCO2), is often determined invasively. An alternate non-invasive approach for the determination of the CvCO2 can be seen in U.S. Pat. No. 6,042,550 and WO 01/62148. In these approaches, exhaled CO2 enriched breathing gases are rebreathed by the subject in subsequent inhalations. As rebreathing of the exhaled breathings gases continues, breath-by-breath, the end tidal CO2 partial pressure (PETCO2) increases until the end capillary blood CO2 partial pressure (PcCO2) is reached. At this point, it is postulated that the end tidal CO2 partial pressure (PETCO2), the alveolar CO2 partial pressure (PACO2), the end capillary blood CO2 partial pressure (PcCO2), and the venous blood CO2 partial pressure (PvCO2) are all equal and that this partial pressure can be converted to the venous CO2 content (CvCO2) for use in the Fick equation.
The need for the determination of the venous blood CO2 content (CvCO2) is eliminated by the use of a differential form of the Fick equation which arises from the following circumstances. As a subject rebreathes exhaled breathing gases, the end tidal CO2 partial pressure (PETCO2) and thus the alveolar CO2 partial pressure (PACO2) and end capillary CO2 content increases. This reduces the venous blood-alveolar CO2 partial pressure differences and because this is the driving force for CO2 elimination in the lungs, CO2 elimination is also reduced. It has been shown that the ratio of the change in CO2 elimination to the change in the end capillary blood CO2 content is equal to the functional cardiac output. See Gedeon A., et al. Med. Biol. Eng. Comp. 18:411-418 (1980). It is set forth in equation form, as follows:                     FCO        =                                                            VCO                2                N                            -                              VCO                2                R                                                                    CcCO                2                R                            -                              CcCO                2                N                                              =                                    Δ              ⁢                                                           ⁢                              VCO                2                                                    Δ              ⁢                                                           ⁢                              CcCO                2                                                                        (        2        )            
In the differential form of the Fick equation, the superscript N indicates values obtained in “normal” breathing conditions. The superscript R indicates values obtained during a short term “reduction” in the CO2 partial pressure difference between that in the alveoli and that in the blood. This results in reduced CO2 transfer in the lungs.
In using the differential form of the Fick equation, a first set of values for VCO2 and CcCO2 are obtained, as in the manner described above, under normal breathing conditions. These are identified by the superscript N. Thereafter, the amount of CO2 in the breathing gases for the subject is increased. This maybe accomplished by a partial re-breathing of exhaled breathing gases. See U.S. Pat. Nos. 5,836,300 or 6,106,480 and published International Patent Appln. WO 98/26710 that employ valve mechanisms, to vary the re-breathed gas volume, for this purpose. Or, this may be accomplished by injecting CO2 into the inhaled breathing gases as described in U.S. Pat. No. 4,608,995. Further possibilities for altering the alveolar CO2 content include varying lung ventilation. This may be accomplished by altering the tidal volume or the respiration rate. Single breath maneuvers such as a deep breath as presented by Mitchell R R in Int J Clin Mon Comp 5:53-64 (1988), inspiratory hold as presented in WO 99/25244, or expiratory hold, may also be used for the purpose.
The CO2 enrichment increases the concentration of CO2 in the alveoli in the lungs and reduces the CO2 partial pressure difference between that of the breathing gases in the lungs and that in the venous blood. As noted above, it is that CO2 partial pressure difference that drives the CO2 gas transfer from venous blood to the breathing gases in the alveoli of the lungs. The reduced CO2 partial pressure difference reduces CO2 gas transfer in the lung and causes an elevation of the CO2 content in the blood downstream of the lung, i.e. in the arterial blood of the subject. In the time interval before the blood with elevated CO2 content circulates through the body and returns to the lungs, the CO2 content of venous blood (CvCO2) entering the lungs can be taken to be the same for both the initial, normal breathing conditions (N) and the subsequent, reduced CO2 partial pressure difference conditions labeled by the superscript R. This similitude permits the factor CvCO2 to be dropped out of the Fick equation when expressed in the differential form as Equation 2 so that the cardiac output is determined by the ratio of the change in released CO2 amounts (VCO2) between the normal (N) and reduced (R) gas exchange conditions to the corresponding change in the end capillary blood CO2 content (CcCO2) in the normal and reduced (R) gas exchange conditions. The need to determine the venous blood CO2 content (CvCO2) from the subject is thus eliminated.
The foregoing approach is also advantageous with ventilated or anesthetized subjects since the alteration of the CO2 content of the breathing gases can be effected by altering the ventilation provided to the subject. In the case of a subject anesthetized with a breathing circuit of the recirculating type, the alteration in CO2 content may be carried out by bypassing the CO2 absorber in the breathing circuit. The CO2 absorber removes CO2 from exhaled breathing gases of the subject thereby allowing the breathing gases to be recirculated to form inspiratory breathing gases for the subject. Bypassing the absorber increases the amount of CO2 in the breathing gases that are recirculated to the subject for inspiration.
While the above described techniques avoid the need to invasively determine venous blood CO2 content, other problems are created. In cases in which a subject is being provided with a fixed volume of breathing gases, an increased re-breathing volume is accompanied by a decreased volume of inspired oxygen. This may produce an undesired reduction in the oxygen content in the blood or require increased oxygen concentrations in the inspired breathing gases, following a cardiac output measurement, to restore oxygen levels in the blood to desired values. Also the tubing required for the large re-breathing volume adds to the size of associated valve systems making them big and bulky when assembled at the very crowded area near the mouth and nose of the subject. Such apparatus also adds to the overall ventilation dead-space volume between the breathing circuit for the subject and the subjects lungs. This increases the amount of ventilation required, adding to the risk of lung distension.
The injection of carbon dioxide into inspired breathing gas overcomes the problems of reduced oxygenation and bulky valve systems, but raises analogous problems. The CO2 is obtained from a gas source and is typically injected using a gas tube. Such a tube is not normally present at the point of care for the subject and adding such a tube, with the accompanying high-pressure regulators and supply conduits, into the already crowded care environment is also undesirable.